Myricetin Alleviates Renal Tubular Oxidative Damage and Calcium Oxalate Deposition via Mediating the Nrf2/ARE Signaling Pathway

Abstract

Hyperoxaluria-induced renal tubular oxidative damage represents a critical factor in kidney stone formation. Myricetin (MYR), a flavonoid compound extracted from the flowers of Abelmoschus manihot, exhibits multiple physiological effects, including antioxidant and anti-inflammatory properties. This study investigated the protective effects of MYR against hyperoxaluria-induced tubular oxidative damage and calcium oxalate (CaOx) deposition mediated through the nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway. Both an ethylene glycol (EG)-induced rat kidney stone model and a CaOx-induced HK-2 cell injury model were employed to examine the renal protective effects of MYR and its underlying mechanisms. MYR attenuated renal tubular damage and injury in EG-treated rats, reduced renal CaOx deposition, and restored the levels of renal function markers (including blood urea nitrogen, creatinine, and N-acetyl-β-d-glucosaminidase) and urinary oxalate, while decreasing renal inflammation. Mechanistically, MYR activated the Nrf2/ARE pathway, upregulating antioxidant enzymes (including heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1), thereby decreasing malondialdehyde levels, and enhancing superoxide dismutase and catalase activities. These effects were significantly reversed by the Nrf2 inhibitor ML385. MYR alleviates tubular oxidative damage and CaOx deposition via the Nrf2/ARE pathway, thus demonstrating potential for kidney stone prevention and treatment. These findings provide a theoretical foundation for developing MYR-based anti-lithiasis drugs.